In situ tailored confining microenvironment for lung cancer spheroids

Area of Science:

• Biomedical Engineering
• Cancer Biology
• Biomaterials Science

Background:

• Extracellular matrix (ECM) mechanical properties and physical confinement critically regulate tumor growth and progression.
• Current 2D and 3D in vitro models struggle to dynamically modulate the cellular microenvironment during culture.
• Controlling the local physical cues experienced by tumor cells remains a significant challenge in cancer research.

Purpose of the Study:

• To develop a 3D culture platform for lung cancer spheroids with tunable mechanical properties and precise spatial control.
• To investigate the impact of adjustable extracellular matrix (ECM) density, stiffness, and confining stress on tumor cell behavior.
• To explore how dynamic microenvironmental modifications influence transcriptional profiles and cell cycle pathways in lung cancer cells.

Main Methods:

• Fabrication of a gelatin-based hydrogel with adjustable density and stiffness for 3D spheroid culture.
• Utilized two-photon mediated bioprinting to create 3D confining microstructures around selected spheroids.
• Analyzed transcriptional profiling of cells to assess responses to varying ECM properties and confining stress.

Main Results:

• Observed diverse transcriptional profiles in lung cancer cells in response to increased ECM density and stiffness.
• Demonstrated that altered confining stress can regulate tumor cells, impacting cell cycle-related pathways.
• Showcased the ability to modify the overall mechanical microenvironment and implement localized adjustments during culture evolution.

Conclusions:

• The developed 3D culture platform enables dynamic modulation of the tumor microenvironment.
• This model provides insights into cell-ECM interactions and their role in tumor progression.
• The platform serves as a valuable tool for studying cancer biology and developing targeted therapies.